The overall objective of this research project is to investigate the role of insulin and glucagon receptors in glucose metabolism. To examine the role of glucagon receptors in the hypersensitivity to glucagon observed in insulin-deprived diabetics, we studied glucagon binding and adenylate cyclase activity in streptozotocin-diabetic rats. We found that liver membranes from untreated diabetic rats had significantly higher glucagon binding and glucagon-stimulated adenylate cyclase activity as compared to controls and that insulin treatment reversed these changes. These data suggest an important role for glucagon receptors in insulin dependent diabetics. In other studies we found that physiologic hyperglucagonemia of 5 hrs duration induced by glucagon infusion in normal rats resulted in significant decreases in hepatic glucagon receptors. The time course of these changes suggest that these changes in glucagon receptor do not account for evanescent nature of glycemic response to glucagon observed in human and animal studies. In studies involving insulin binding to monocytes and insulin-mediated glucose uptake (insulin clamp) we found that patients with isolated growth hormone deficiency have significantly increased insulin binding to monocytes and glucose uptake and that growth hormone treatment resulted in normalization of these changes.